Yap/Taz are required for establishing the cerebellar radial glia scaffold and proper foliation

被引:9
作者
Hughes, Lucinda J. [1 ,2 ]
Park, Raehee [1 ]
Lee, Min Jung [1 ]
Terry, Bethany K. [1 ,2 ]
Lee, David J. [1 ]
Kim, Hansol [1 ]
Cho, Seo-Hee [1 ]
Kim, Seonhee [1 ]
机构
[1] Temple Univ, Lewis Katz Sch Med, Dept Anat & Cell Biol, Shriners Hosp Pediat Res Ctr, 3500 North Broad St, Philadelphia, PA 19140 USA
[2] Temple Univ, Grad Program Biomed Sci, Lewis Katz Sch Med, Philadelphia, PA 19140 USA
基金
美国国家卫生研究院;
关键词
HIPPO-YAP PATHWAY; PROGENITOR CELLS; BERGMANN GLIA; MEDULLOBLASTOMA; REGENERATION; FATE; TAZ; DOWNSTREAM; GENERATION; EXPRESSION;
D O I
10.1016/j.ydbio.2019.10.002
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Yap/Taz are well-established downstream effectors of the Hippo pathway, known to regulate organ size by directing proliferation and apoptosis. Although the functions of Yap/Taz have been extensively studied, little is known about their role in brain development. Here, through genetic ablation, we show that Yap/Taz are required for cerebellar morphogenesis. Yap/Taz deletion in neural progenitors causes defects in secondary fissure formation, leading to abnormal folia development. Although they seemed very likely to serve an important function in the development of cerebellar granule cell precursors, Yap/Taz are dispensable for their proliferation. Furthermore, Yap/Taz loss does not rescue the medulloblastoma phenotype caused by constitutively active Smoothened. Importantly, Yap/Taz are highly expressed in radial glia and play a crucial role in establishing the radial scaffold and cellular polarity of neural progenitors during embryogenesis. We found that Yap/Taz are necessary to establish and maintain junctional integrity of cerebellar neuroepithelium as prominent junction proteins are not maintained at the apical junction in the absence of Yap/Taz. Our study identifies a novel function of Yap/Taz in cerebellar foliation and finds that they are required to establish the radial glia scaffold and junctional stability.
引用
收藏
页码:150 / 162
页数:13
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